The primary objective is to assess the safety of the addition of venetoclax to reduced intensity conditioning for HLA-matched and haploidentical combined HSC and kidney transplantation as measured by stable full donor hematopoiesis and absence of CTCAE grade IV or V toxicity attributable to venetoclax.

Recipient Inclusion Criteria:

• Patient ages 18-70
• Underlying hematological malignancy which is deemed as being potentially curable with allogeneic bone marrow or PBSC transplantation by the BMT voting team.
• Hematological malignancies include, but are not limited to: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, multiple myeloma (MM), myelodysplastic syndrome (MDS. Patient should be in a partial (PR) or complete remission (CR) at the time of the transplant.
• Existence of an HLA-matched or haploidentical relative who passes standard donor evaluations for bone marrow and kidney donation
• LVEF > 40% as measured by echocardiography or MUGA
• FEV1, FVC, and DLCO > 50% of predicted as measured by standard PFTs
• Total bilirubin < 2.0 (unless diagnosis of Gilbert's or hemolysis is made) and AST, ALT, alkaline phosphatase all < 5x institutions upper limit of normal
• ABO compatibility in the host vs. graft direction
• Men and women of reproductive potential must agree to use a reliable method of birth control during the treatment, and women should do so for a period of 1 year following the transplant.
• Participants should be on dialysis or have a CrCl ≤ 35 ml/min
• Life expectancy greater than 6 months
• Recipient ability to understand and provide informed consent

Donor Inclusion Criteria:

• HLA matched or haploidentical relative as defined by 3/6, 4/6, or 5/6 HLA-matched at HLA -A, -B, or -DRB1 who is 18-70 years of age

• ECOG performance status 0 or 1

• Excellent health per conventional pre-donor history (medical and psychosocial evaluation)

  • Acceptable laboratory parameters (hematology in normal or near-normal range; liver function < 3 times the upper limit of normal and normal creatinine)

• Compatible ABO blood group

• Negative donor lymphocyte cross match

• No positive testing for active viral infection (Hepatitis B, Hepatitis C, HIV)

• Donor ability to understand and provide informed consent

• Meets standard institutional criteria for both bone marrow or peripheral blood stem cell (PBSC) and kidney donation

Exclusion Criteria:

• Active serious infection
• Participation in other investigational drug use at the time of enrollment
• Positivity for active infection with HIV, HCV, or HBV
• ABO blood group incompatibility in the host-vs-graft direction